The Nasal Microbiome in ANCA-Associated Vasculitis: Picking the Nose for Clues on Disease Pathogenesis

Purpose of Review The onset and progression of small vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies has been linked to microbial infections. Here, we provide a brief overview of the association of nasal colonization of Staphylococcus aureus with ANCA-associated vasculitis (AAV) and discuss several recent studies mapping the nasal microbiome in AAV patients in particular. Recent Findings Nasal microbiome studies revealed dysbiosis as a common trait in active AAV which tends to normalize upon immunosuppressive treatment and quiescent disease. However, due to differences in study design, patient selection, and methodology, the reported microbiome profiles differ considerably precluding conclusions on causal relationships. Summary The microbiome is an emerging area of research in AAV warranting further investigation. Ideally, such studies should be combined with mechanistic studies to unravel key elements related to host-microbe interactions and their relevance for AAV pathogenesis.

Distinguishing active from quiescent disease in ANCA-associated vasculitis using attenuated total reflection Fourier-transform infrared spectroscopy

The current lack of a reliable biomarker of disease activity in anti-neutrophil cytoplasmic autoantibody (ANCA) associated vasculitis poses a significant clinical unmet need when determining relapsing or persisting disease. In this study, we demonstrate for the first time that attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy offers a novel and functional candidate biomarker, distinguishing active from quiescent disease with a high degree of accuracy. Paired blood and urine samples were collected within a single UK centre from patients with active disease, disease remission, disease controls and healthy controls. Three key biofluids were evaluated; plasma, serum and urine, with subsequent chemometric analysis and blind predictive model validation. Spectrochemical interrogation proved plasma to be the most conducive biofluid, with excellent separation between the two categories on PC2 direction (AUC 0.901) and 100% sensitivity (F-score 92.3%) for disease remission and 85.7% specificity (F-score 92.3%) for active disease on blind predictive modelling. This was independent of organ system involvement and current ANCA status, with similar findings observed on comparative analysis following successful remission-induction therapy (AUC > 0.9, 100% sensitivity for disease remission, F-score 75%). This promising technique is clinically translatable and warrants future larger study with longitudinal data, potentially aiding earlier intervention and individualisation of treatment.

Clinico-pathological associations of serum VCAM-1 and ICAM-1 levels in patients with lupus nephritis

Objective We investigated the clinico-pathological associations of serum VCAM-1 and ICAM-1 levels in patients with biopsy-proven Class III/IV±V lupus nephritis (LN). Methods Serum VCAM-1 and ICAM-1 levels were determined by ELISAs. Sera from patients with non-renal SLE or non-lupus chronic kidney disease (CKD), and healthy subjects served as controls. Results Seropositivity rate for VCAM-1 and ICAM-1 was 93.10% and 37.93% respectively at the time of nephritic flare, and 44.83% and 13.79% respectively at remission, with both showing higher levels during flare ( P < 0.05, for both). VCAM-1 level correlated with proteinuria, serum creatinine, and anti-dsDNA antibodies, and inversely correlated with C3. VCAM-1 level also correlated with leukocyte infiltration and fibrinoid necrosis/karyorrhexis scores in active LN kidney biopsies. ICAM-1 level correlated with proteinuria, but not anti-dsDNA or C3, nor histopathological features. VCAM-1 level increased 4.5 months before renal flare, while ICAM-1 increase coincided with flare, and both decreased after treatment. ROC analysis showed that VCAM-1 distinguished active LN from healthy subjects, LN in remission, active non-renal lupus, and CKD (ROC AUC of 0.98, 0.86, 0.93 and 0.90 respectively). VCAM-1 level in combination with either proteinuria or C3 was superior in distinguishing active LN from remission compared to the measurement of individual markers. Serum ICAM-1 level distinguished active LN from healthy subjects and LN patients in remission (ROC AUC of 0.75 and 0.66 respectively), but did not distinguish between renal versus non-renal lupus. ICAM-1 level in combination with markers of endothelial cell activation (syndecan-1, hyaluronan and thrombomodulin) was superior to proteinuria, anti-dsDNA, or C3 in distinguishing active LN from quiescent disease. Conclusion Our findings suggest potential utility of serum VCAM-1 and ICAM-1 in clinical management. Monitoring VCAM-1 may facilitate early diagnosis of flare. Combining selected biomarkers may be advantageous in diagnosing active LN. VCAM-1 may have a pathogenic role in renal parenchymal inflammation in active LN.

Recommendations for COVID-19 Vaccination in People with Rheumatic Disease: Developed by the Singapore Chapter of Rheumatologists

AimPeople with rheumatic diseases (PRD) remain vulnerable in the era of the COVID-19 pandemic. We formulated recommendations to meet the urgent need for a consensus for vaccination against SARS-CoV-2 in PRD.MethodsSystematic literature reviews were performed to evaluate (1) outcomes in PRD with COVID-19; (2) efficacy, immunogenicity and safety of COVID-19 vaccination; and (3) published guidelines/recommendations for non-live, non-COVID-19 vaccinations in PRD. Recommendations were formulated based on the evidence and expert opinion according to the Grading of Recommendations Assessment, Development and Evaluation methodology.ResultsThe consensus comprises two overarching principles and seven recommendations. Vaccination against SARS-CoV-2 in PRD should be aligned with prevailing national policy and should be individualized through shared decision between the healthcare provider and patient. We strongly recommended that eligible PRD and household contacts be vaccinated against SARS-CoV-2. We conditionally recommended that the COVID-19 vaccine be administered during quiescent disease if possible. Immunomodulatory drugs, other than rituximab, can be continued alongside vaccination. We conditionally recommended that the COVID-19 vaccine be administered prior to commencing rituximab if possible. For patients on rituximab, the vaccine should be administered a minimum of 6 months after the last dose and/or 4 weeks prior to the next dose of rituximab. Post-vaccination antibody titres against SARS-CoV-2 need not be measured. Any of the approved COVID-19 vaccines may be used, with no particular preference.ConclusionThese recommendations provide guidance for COVID-19 vaccination in PRD. Most recommendations in this consensus are conditional, reflecting a lack of evidence or low-level evidence. (words 247)

Successful Use of Tocilizumab in a Child with Systemic Juvenile Idiopathic Arthritis

Objective of the Paper: To demonstrate a case of successful use of tocilizumab in a child with systemic juvenile idiopathic arthritis (JIA). Key Points. A clinical variant of JIA is systemic arthritis (systemic JIA). Currently, management of systemic JIA includes tocilizumab, a recombinant humanised anti–interleukin-6 receptor monoclonal antibody. The article describes a case of successful use of tocilizumab in a child with systemic JIA after inefficient therapy with glucocorticosteroids and methotrexate. Conclusion. Systemic JIA is the severest clinical JIA variant. Tocilizumab allows achieving the quiescent disease stage where the standard therapy with glucocorticosteroids and methotrexate is ineffective. Keywords: system arthritis, juvenile idiopathic arthritis, tocilizumab, children.

OP0204 LUPUS COMPREHENSIVE DISEASE CONTROL IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: APPLICATION OF A NEW INDEX

Background:The main outcomes in SLE patients management are represented by the remission achievement and chronic damage prevention. Even though activity and damage are intimately connected, to date indices including both these outcomes are not available.Objectives:In the present study, we aimed at assessing the application of a new index, the Lupus comprehensive disease control (LupusCDC), including disease activity and chronic damage progression.Methods:We performed a longitudinal analysis, including SLE patients according to ACR 1997 criteria, followed-up in the period between January 2014 and December 2018, and with at least one visit per year. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and three different remission levels were evaluated, as reported in Table 1 (1).Table 1.Remission levels considered in the study (1).Remission levelDefinitionComplete Remission(CR)No clinical and serological activity (SLEDAI-2K=0) in corticosteroid-free and immunosuppressant-free patients (antimalarials allowed)Clinical remission off-corticosteroids(ClR-GCoff)Serological activity with clinical quiescent disease according to SLEDAI-2K in corticosteroid-free patients (stable immunosuppressive therapy and antimalarials allowed)clinical remission on-corticosteroids(ClR-GCon)Clinical quiescent disease according to SLEDAI-2K in patients on prednisone 1–5 mg/day (stable immunosuppressants and antimalarials allowed)Chronic damage was registered according to SLICC damage index (SDI). All the patients were evaluated at baseline (T0) and every 12 months (T1, T2, T3, T4). At each time-point, we calculated the prevalence of LupusCDC, defined as remission achievement plus absence of chronic damage progression in the previous one year. We calculated this outcome including separately the different remission levels.Results:According with inclusion criteria, 172 SLE patients were evaluated in the present analysis [M/F 16/156, median age 49 years (IQR 16.7), median disease duration 180 months (IQR 156)]. At first assessment, we observed a mean±SD SDI value of 0.7±1.1. In details, 56 patients (32.5%) showed damage in at least one organ/system and the presence of damage was significantly associated with age (p<0.0001, r=0.3) and disease duration (p=0.0003, r=0.3). During the follow-up, we observed a significant increase in SDI values compared with T0 (T1: mean±DS 0.8±1.3, p<0.0001; T2: 0.8±1.4, p<0.0001; T3: 0.9±1.4 p=0.0001; T4: 1.0±1.5 p<0.0001).In figure 1A and 1B we reported the proportion of patients achieving the different levels of remission and LupusCDC, respectively. In particular, the LupusCDC definition including CR was the most frequently detected in all time-points evaluated (T1: 18.0%; T2: 31.9%; T3: 27.9%; T4: 24.4%), with a significant difference at T2 [LupusCDC(CR)versusLupusCDC(ClR-GCoff), p=0.0002; LupusCDC(CR)versusLupusCDC(ClR-GCon) p=0.0002)], T3 [LupusCDC(CR)versusLupusCDC(ClR-GCoff), p=0.03; LupusCDC(CR)versusLupusCDC(ClR-GCon) p=0.006], T4 [LupusCDC(CR)versusLupusCDC(ClR-GCon), p=0.002]. No significant differences were found when comparing the prevalence of different remission levels and the prevalence of LupusCDC including the corresponding remission.Conclusion:In the present analysis we proposed for the first time a new index including disease activity and chronic damage, in order to evaluate the proportion of SLE patients reaching a comprehensive disease control. We found that CR is most frequently associated with the absence of damage progression.References:[1]Zen M et al. Ann Rheum Dis 2017.Disclosure of Interests:Fulvia Ceccarelli: None declared, Giulio Olivieri: None declared, Lorenzo Dominici: None declared, Alessandra Ida Celia: None declared, enrica cipriano: None declared, Cristina Garufi: None declared, Silvia Mancuso: None declared, Francesco Natalucci: None declared, Valeria Orefice: None declared, Carlo Perricone: None declared, Carmelo Pirone: None declared, viviana antonella pacucci: None declared, Francesca Morello: None declared, Simona Truglia: None declared, Francesca Miranda: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi

Pregnancy and medications in inflammatory bowel disease

IBD affects patients at a significant time in their lives, often coinciding with family planning or pregnancy. While advances in IBD therapies have afforded women greater opportunities for successful conception and pregnancy outcomes, there still remains considerable maternal fear surrounding continuation of treatment throughout pregnancy. With the exception of methotrexate, most IBD drugs are safe and well-tolerated during pregnancy and are not associated with significant risk of adverse fetal or pregnancy outcomes. Furthermore, the current evidence overwhelmingly suggests that good control of disease activity and clinical remission at time of conception are the greatest prognostic factors for an uncomplicated pregnancy and maintenance of quiescent disease during gestation. Management of pregnant IBD patients should involve frank discussions with the mother and family about fears or concerns surrounding the impact of IBD on pregnancy. Mothers should be supported and counselled carefully on the safety and importance of adherence to therapy in maintaining remission. Optimal management of these women requires an inter-disciplinary team effort, involving the general practitioner, in close consultation and discussion with both gastroenterologists and obstetricians.